Daniel J. Sheehan

Cutaneous epithelioid angiomatous nodule: a case series and proposed classification.

Cutaneous epithelioid angiomatous nodule is a peculiar and recently recognized vascular proliferation. Clinically, these lesions affect different areas of the body and histologically are characterized by a well-circumscribed, mainly unilobular, solid proliferation of endothelial cells with prominent epithelioid features. The cytoplasm is abundant and eosinophilic, and many of the neoplastic cells contain prominent vacuoles. Inflammatory infiltrates are variable. All the cases reported thus far have followed a benign course. We report 10 additional cases of this curious entity, including 2 which presented in an eruptive fashion and 5 that were located on the head and neck. We also discuss the histological differential diagnoses with other epithelioid proliferations and propose categorization within the spectrum of epithelioid hemangioma.

Transglutaminases: the missing link in nephrogenic systemic fibrosis.

Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), occurs in renal failure patients after gadolinium contrast exposure. The fibrosis of the dermis and subcutaneous septae accompanies fibrosis of other organs, including the heart, liver, lungs, and muscle. The fibrotic skin demonstrates increased dermal collagen, fibroblasts, and mucin. The mechanism by which gadolinium is associated with fibrosis is not known.We tested the hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in the organs, including skin, of renal failure patients exposed to gadolinium contrast.We performed immunohistochemical studies using antibodies to transglutaminase-2, factor XIIIa, transglutaminase isopeptide, and the histiocyte marker CD68 on five archived skin biopsies of NSF. The results indicate that the dermal fibroblasts and histiocytes of NSF express transglutaminase-2, CD68, factor XIIIa, and transglutaminase isopeptide, indicating increased expression and/or activation of transglutaminases in NSF. We recommend further research into the use of transglutaminase inhibitors in the treatment and prevention of NSF.

ABNORMAL AQUAPORIN-3 PROTEIN EXPRESSION IN HYPERPROLIFERATIVE SKIN DISORDERS

Non-melanoma skin cancers (NMSCs) and psoriasis represent common hyperproliferative skin disorders, with approximately one million new NMSC diagnoses each year in the United States alone and a psoriasis prevalence of about 2% worldwide. We recently demonstrated that the glycerol channel, aquaporin-3 (AQP3) and the enzyme phospholipase D2 (PLD2) interact functionally in epidermal keratinocytes of the skin to inhibit their proliferation. However, others have suggested that AQP3 is pro-proliferative in keratinocytes and is upregulated in the NMSC, squamous cell carcinoma (SCC). To evaluate the AQP3/PLD2 signaling module in skin diseases, we determined their levels in SCC, basal cell carcinoma (BCC) and psoriasis as compared to normal epidermis. Skin biopsies with the appropriate diagnoses (10 normal, 5 SCC, 13 BCC and 10 plaque psoriasis samples) were obtained from the pathology archives and examined by immunohistochemistry using antibodies recognizing AQP3 and PLD2. In normal epidermis AQP3, an integral membrane protein, was localized mainly to the plasma membrane and PLD2 to the cell periphery, particularly in suprabasal layers. In BCC, AQP3 and PLD2 levels were reduced as compared to the normal-appearing overlying epidermis. In SCC, AQP3 staining was “patchy,” with areas of reduced AQP3 immunoreactivity exhibiting positivity for Ki67, a marker of proliferation. PLD2 staining was unchanged in SCC. In psoriasis, AQP3 staining was usually observed in the cytoplasm rather than in the membrane. Also, in the majority of psoriatic samples, PLD2 showed weak immunoreactivity or aberrant localization. These results suggest that abnormalities in the AQP3/PLD2 signaling module correlate with hyperproliferation in psoriasis and the NMSCs.

The effect of sunless tanning on behavior in the sun: a pilot study.

Background: In the United States, indoor tanning is a booming industry and contributes to the ultraviolet light (UVL) burden that ultimately leads to skin cancer. “Sunless” tanning methods that avoid UVL exposure may represent a safe alternative. However, the effects of sunless tanning methods on ultraviolet light-related behaviors have never been investigated. Methods: Anonymous survey of 121 individuals who underwent a spray-on sunless tanning treatment between February and May 2004. Results: Women completed 107 surveys. Men completed 14 surveys. The majority of individuals reported that they had not or would not change their time spent outdoors or their sunscreen use as a result of undergoing sunless tanning. However, 73% of individuals who had used UVL tanning beds said they had decreased or would decrease their UVL tanning bed use. Conclusion: Sunless tanning is associated with a self-reported decrease in traditional UVL tanning bed use among tanning bed users. Physicians should advocate the use of sunless tanning to their patients who use traditional UVL tanning beds as a means of decreasing their UVL exposure and cancer risk.

Retiform hemangioendotheliomas usually do not express D2-40 and VEGFR-3

Retiform hemangioendothelioma (RH) is a rare vascular neoplasm most often occurring in the limbs of middle-aged females. This entity is characterized by infiltrative vascular spaces arranged in a pattern similar to the rete testis. RH differs from angiosarcoma by lacking cytologic atypia and high mitotic rates. This neoplasm frequently recurs but rarely metastasizes. RH tumor cells react with vascular endothelial markers CD31, CD34, and factor VIII-related antigen. A review of the English literature provides only one attempt at staining RH with D2-40, a marker of endothelium of lymphatic vessels, which was negative, and one reported staining of RH with lymphatic endothelial marker VEGFR-3, which was positive. The etiology of RH is unknown. RH has previously been considered closely related to Dabska tumors, which are positive for lymphatic endothelial marker D2-40. We stained 4 RHs with mouse monoclonal antibodies against D2-40 and CD31 and 3 of the 4 RHs with vascular endothelial growth factor receptor 3 (VEGFR-3), to further evaluate whether RH had lymphatic differentiation, in addition to vascular differentiation. Three of the 4 RH biopsies failed to demonstrate D2-40, none expressed VEGFR-3, whereas CD31 was strongly positive, suggesting that RH is a vascular entity which usually does not have lymphatic differentiation, but may rarely express D2-40.

Cutaneous draining sinus tract of odontogenic origin: unusual presentation of a challenging diagnosis.

A 44-year-old woman presented with a chronically draining lesion on her cheek just lateral to the nasofacial sulcus. The lesion was refractory to treatment with oral antibiotics. Physical examination revealed poor dentition, and a panoramic radiograph demonstrated periapical abscesses in the maxillary right lateral incisor and canine. A diagnosis of cutaneous fistula of odontogenic origin was made, and the patient was treated with tooth extraction. The cutaneous fistula subsequently resolved. Intraoral examinations and radiographs are critical for making the diagnosis of cutaneous draining sinus tract of odontogenic origin. Many patients undergo unnecessary surgical therapies before having the correct diagnosis made, but root canal therapy or surgical extraction is the treatment of choice. A dental origin must be considered for any chronically draining sinus of the face or neck.

Generalized granuloma annulare as an initial manifestation of chronic myelomonocytic leukemia: A report of 2 cases

Granuloma annulare is a dermatologic condition of unknown etiology that has been associated with systemic diseases and reported to be a paraneoplastic manifestation. Two patients with generalized granuloma annulare as an initial manifestation of chronic myelomonocytic leukemia are herein described. We suggest that chronic myelomonocytic leukemia should be added to the list of systemic diseases associated with generalized granuloma annulare.

Video game induced knuckle pad

Abstract:  Controversy and concern surround the video game playing fascination of children. Scientific reports have explored the negative effects of video games on youth, with a growing number recognizing the actual physical implications of this activity. We offer another reason to discourage childrens focus on video games: knuckle pads. A 13‐year‐old black boy presented with an asymptomatic, slightly hyperpigmented plaque over his right second distal interphalangeal joint. A punch biopsy specimen confirmed knuckle pad as the diagnosis, and a traumatic etiology from video game playing was suspected. Knuckle pads can be painful, cosmetically unappealing, and refractory to treatment. They can now be recognized as yet another potential adverse consequence of chronic video game playing.

The Role of Sirolimus in the Prevention of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients

Skin cancers are common in organ transplant recipients (OTRs). In this review, we discuss the epidemiology of and risk factors for cutaneous neoplasms, particularly squamous cell carcinoma (SCC) in OTRs. The pathogenesis of SCC is reviewed, as well as the potential mechanisms for tumor progression and metastasis associated with two commonly used immunosuppressive medications: tacrolimus and cyclosporine. Finally, we discuss the mechanism of action and potential preventative use of sirolimus, a member of a newer class of immunosuppressants, the mammalian target of rapamycin inhibitors. The authors have indicated no significant interest with commercial supporters.

Lasp1 gene disruption is linked to enhanced cell migration and tumor formation

Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1(-/-) mice compared with Lasp1(+/+) controls. Embryonic fibroblasts (MEFs) derived from Lasp1(-/-) mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion, and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased about twofold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1(-/-) MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells compared with cell lines reveals distinct differences in mechanisms of motility and attachment in these models.